Pancreatic cancer classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S [2]

Overview

Pancreatic cancers can be classified based on the production of hormones into exocrine and endocrine cancers. Pancreatic exocrine tumors include different types such as Adenocarcinoma, acinar cell carcinoma, adenosquamous carcinoma and pancreatoblastomas. Pancreatic endocrine tumors include insulinomas, glucagonomas, VIPomas, somatostatinomas and Ppomas. Additionally, early-onset pancreatic cancer is defined as pancreatic cancer that occurs before the age of 50 years.

Pancreatic cancers can be classified based on the production of hormones into exocrine and endocrine cancers:


Types of Pancreatic Cancers
Pancreatic Exocrine Cancers	Pancreatic Endocrine Cancers (Pancreatic Neuroendocrine Tumours)
Adenocarcinoma	Gastrinoma
Acinar cell carcinoma	Glucagonoma
Adenosquamous carcinoma	Insulinoma
Giant cell tumor	Nonfunctional islet cell tumor
Intraductal papillary mucinous neoplasm (IPMN)	Somatostatinoma
Mucinous cystadenocarcinoma	Vasoactive intestinal peptide releasing tumor (VIPoma)
Pancreatoblastoma
Serous cystadenocarcinoma
Solid and pseudopapillary tumours


Types of Pancreatic Intraepithelial Neoplasia (PanIN)
PanIN 1 (low grade)
Minimal degree of atypia
Subclassified into PanIN 1A: absence of micropapillary infoldings of the epithelium; and 1B, presence of micropapillary infoldings of the epithelium
PanIN 2 (intermediate grade)
Moderate degree of atypia, including loss of polarity, nuclear crowding, enlarged nuclei, pseudostratification, and hyperchromatism
Mitosis is rarely seen
PanIN 3 (high grade/carcinoma in situ)
Severe atypia, with varying degrees of cribriforming, luminal necrosis, and atypical mitosis
Contained within the basement membrane

Functional Pancreatic Neuroendocrine Tumors and their Characteristics are mentioned in the following table:^[2]


Functional Pancreatic Neuroendocrine Tumors and their Characteristics
Tumor type and syndrome	Location in pancreas	Signs and symptoms	Circulating biomarkers
Insulinoma (Whipple’s triad)	Head, body, tail (evenly distributed)	Hypoglycemia, dizziness, sweating, tachycardia, tremulousness, confusion, seizure	CgA and CgB, insulin inappropriate for blood glucose level, proinsulin, C-peptide
Gastrinoma (Zollinger–Ellison)	Gastrinoma triangle Often extrapancreatic (duodenal); can be found anywhere in gland	Gastric acid hypersecretion, peptic ulcer, diarrhea, esophagitis, epigastric pain	CgA, gastrin, PP (35%)
VIPoma (Verner– Morrison syndrome, WDHA)	Distal pancreas (body and tail) Often spread outside pancreas	Watery diarrhea, hypokalemia, achlorhydria (or acidosis)	CgA, VIP
Glucagonoma	Body and tail of pancreas Often large and spread outside pancreas	Diabetes (hyperglycemia), necrolytic migratory erythema, stomatitis, glossitis, angular cheilitis	CgA, glucagon, glycentin
Somatostatinoma	Pancreatoduodenal groove, ampullary, periampullary	Gallstones, diabetes (hyperglycemia), steatorrhea	CgA, somatostatin
Ppoma	Head of pancreas	None	CgA, PP

**Key

CgA- Chromogranin A

CgB- Chromogranin B

PP- Pancreatic polypeptide


TNM Classification for Pancreatic Cancer:
Primary tumor
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	Carcinoma in situ
T1	Tumor limited to the pancreas, ≤2 cm in greatest dimension
T2	Tumor limited to the pancreas, >2 cm in greatest dimension
T3	Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery
T4	Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor)
Regional lymph nodes
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Regional lymph node metastasis
Distant metastases
MX	Distant metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis

↑ ^1.0 ^1.1 ^1.2 Bond-Smith G, Banga N, Hammond TM, Imber CJ (2012). “Pancreatic adenocarcinoma”. BMJ. 344: e2476. doi:10.1136/bmj.e2476. PMID 22592847.
↑ Ryan DP, Hong TS, Bardeesy N (2014). “Pancreatic adenocarcinoma”. N Engl J Med. 371 (11): 1039–49. doi:10.1056/NEJMra1404198. PMID 25207767.
↑ Seufferlein T, Bachet JB, Van Cutsem E, Rougier P, ESMO Guidelines Working Group (2012). “Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up”. Ann Oncol. 23 Suppl 7: vii33–40. doi:10.1093/annonc/mds224. PMID 22997452.